The present invention relates generally to electroporation for drug and gene delivery and pertains more particularly to an electrode assembly for an apparatus for and a method of trans-surface delivery of genes, drugs, and other molecules through tissue surfaces for both therapeutic and cosmetic purposes.
The medical community has in recent years been investigating electroporation as a method of trans-surface delivery of drugs, genes such as DNA, portions of DNA, chemical agents, or other molecules without physical penetration or invasion of the tissue surface. This method can be used for the application of molecules for the therapeutic treatment of cancer or for cosmetic treatment of skin blemishes and abnormalities such as wrinkles and age spots. It can also be used for gene therapy. This method involves the electroporation of the tissue surface through the application of an electrical field by means of electrodes on the tissue surface. Electroporation can make tissue permeable to enable the molecules to pass through the tissue surface and more readily enter the tissue. Electroporation can also make cell tissue permeable to enable the molecules to enter preselected cells in the tissue without damaging them.
The molecules to be introduced into the cells are placed in close proximity to the cells, either in the interstitial tissue surrounding the cells or in a fluid medium containing the cells. The field is applied at a predetermined strength and duration in order to make the walls of the tissue surface transiently permeable to permit the molecules to pass through the tissue surface into the underlying tissue.
The voltage that must be applied to induce electroporation is proportional to the distance between the electrodes. When the space between the electrodes is too great, the generated electric field penetrates deep into the tissue where it causes unpleasant nerve and muscle reaction. The applicants have discovered electrode arrays and configurations that maximize the field strength and reduce the unpleasant nerve and muscle reaction.
Electroporation can be carried out by a sophisticated electroporation system having programmable power sequence and duration programmed in. For example, a suitable system is disclosed in U.S. Pat. No. 5,869,326 issued Feb. 9, 1999 entitled ELECTROPORATION EMPLOYING USER-CONFIGURED PULSING SCHEME, which is incorporated herein by reference as though fully set forth. Broadly, that invention concerns an electroporation apparatus for and method of generating and applying an electric field according to a user-specified pulsing scheme. One example of such a pulsing scheme includes a low voltage pulse of a first duration, immediately followed by a high voltage pulse of a second duration, and immediately followed by a low voltage pulse of a third duration. The low voltage field acts to accumulate molecules at the tissue surface, the appropriately high voltage field acts to create an opening in the tissue surface, and the final low voltage field acts to move the molecules through the tissue surface.
While electroporation provides new pathways through the tissue surface for passages of molecules, it does not provide a needed driving force to those molecules to move them through the tissue surface or through the tissue to the cell site. As a result, it is desirable to combine electroporation with techniques for providing a driving force. Iontophoresis alone, wherein low voltage is applied between widely spaced electrodes for a long period of time, can transport charged molecules through existing pathways such as hair follicles and sweat glands. However, the volumes of molecules transported for a unit of time is very small, and insufficient for many applications. Combining electroporation and iontophoresis can increase the amount transported initially while the created pathways are open. The paths created by the electroporation stay open for a only short period of time and then close.
One example of a surface for the trans-surface delivery of molecules is the skin or the stratum corneum (SC). The SC consists of a thin layer of dead cells with a high electrical resistance which presents a major obstacle to the administration of drugs and genes transdermally. However, this layer can be perforated by the administration of short high voltage pulses, which create a dielectric breakdown of the SC forming pores which can allow the passage of molecules.
There is a need for improved electrodes that maximize areas of desired field strength for tissue surfaces to which to apply electroporation which surfaces vary by their size, shape, location, porosity, and accessability, among others. It is desirable that an electrode assembly for an apparatus for and a method of trans-surface molecular delivery be available to efficiently accommodate a wide variety of these tissue surfaces.
It is the primary object of the present invention to provide an improved electrode assembly for an apparatus for and a method of trans-surface molecular delivery which maximize areas of desired field strength for tissue surfaces to which to apply electroporation.
In accordance with the primary aspect of the present invention, electrodes configured to apply to tissue surface are configured to minimize the conductive areas and areas of low field strength while maximizing the areas of desired field strength.
In accordance with the method molecules are brought into physical contact with the tissue surface, an electrode is contacted with the tissue surface, and an electric field is applied to the tissue surface by means of the electrode. This forms pores in the tissue surface. Then a driving force is applied to the tissue surface forcing the molecules through the tissue surface into the underlying tissue.